Extended periods of waking result in cognitive impairments in humans, rats, and flies. Sleep homeostasis, the increase in sleep observed following sleep loss, is believed to counter the negative effects of prolonged waking by restoring vital biological processes that are degraded during sleep deprivation. Unfortunately, precisely which processes need restoration remains a matter of speculation and debate. Given that sleep disturbances are increasingly recognized as contributing to cognitive impairment in patients with neurological disorders, identifying pathways that are degraded during waking and restored during sleep may enhance our ability to understand neuronal processes during both health and disease. We have found that short-term memory deficits resulting from sleep loss can be reversed during sleep deprivation to a level only observed following a full night's sleep. Specifically, functional restoration of short-term memory can be achieved in an otherwise wake, behaving animal by altering a single neuronal structure. With that in mind, we will evaluate the role of sleep loss on both the acquisition of short-term memory and the ability to consolidate long-term memories (LTM) after post-training sleep deprivation. We hypothesize that genes that prevent declines in short-term memory during sleep deprivation and/or preserve the ability to consolidate long-term memories LTM after post- training sleep deprivation are strong candidates for playing a role in sleep restoration. PUBLIC HEALTH RELEVANCE: Sleep disturbances are increasingly recognized as contributing to cognitive impairment in patients with neurological disorders. Identifying pathways that are degraded during waking and restored during sleep may enhance our ability to understand neuronal processes during both health and disease.